For maximum efficiency, the lipids within circulating lipopro-teins should be taken up only by those cells that require them for membrane formation (e.g., dividing cells), steroid hormone synthesis (e.g., endocrine cells), energy production (e.g., muscle cells), or storage (adipose cells, endocrine cells). The targeting of lipoprotein lipids to appropriate cells is accomplished in one of two ways: (1) local, partial extracellular hydrolysis of core triglycerides followed by transport proteinmediated uptake of the released fatty acids or (2) the regulated expression of cell-surface lipoprotein receptors that mediate the direct uptake of lipoprotein lipids.
The first targeting mechanism, for example, supplies cells with fatty acids for use as an energy source in muscle and for storage in adipose tissue. The extracellular enzyme lipoprotein lipase is attached by glycosaminoglycan (GAG) chains to the blood-facing surface of endothelial cells in these tissues. Fatty acids released from the hydrolysis of core triglycerides in VLDL and chylomicrons then cross the vessel wall and enter underlying cells through fatty acid transporters such as FATPs and CD36 (see Figure 18-10a). This process results in the delivery of fatty acids to the cells concomitant with remodeling of the lipoprotein particles.
The expression of various lipoprotein receptors by different tissues also ensures that lipids are delivered to cells that need and can use them. In every case of receptor-
facilitated delivery, cholesteryl esters and triglycerides in the lipoprotein core must cross two topological barriers to enter the cytoplasmic space: the phospholipid monolayer shell of the lipoprotein particle and the cell's bilayer plasma membrane. At some point in the lipid-delivery process, the ester-ified transport forms of the core lipids must be hydrolyzed to unesterified forms (cholesterol, fatty acids) to be usable by the importing cells. Cells have evolved two distinct mechanisms for receptor-facilitated uptake of lipids in lipoprotein cores: receptor-mediated endocytosis of entire lipoprotein particles and selective lipid uptake of certain lipid components of lipoprotein particles.
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